An unusual presentation of metastatic prostate cancer in a 44‐year‐old man: A case report and review of the literature

Abstract Prostate cancer is one of the two most common non‐cutaneous cancers in men. Its presentation might be with unusual symptoms and cause the wrong initial diagnosis. This case report discusses a rare neurologic manifestation of advanced metastatic cancer in a low‐risk man. He had been receiving treatment for multiple sclerosis incorrectly due to unusual manifestations such as claudication and pelvic, leg, and shoulder pain. The patient underwent a whole‐body bone scan and then a transrectal ultrasound‐guided biopsy, which confirmed metastatic prostate cancer with a Gleason score between 7/10 and 10/10 in all samples. Following treatment with chemotherapeutic injections (docetaxel), luteinizing hormone‐releasing hormone (LHRH) analogous (Zoladex), and testosterone‐suppressing tablets (abiraterone), the disease has been under control and prostate‐specific antigen (PSA) level has decreased significantly. The most common sites of metastasis are regional lymph nodes, bones, and lungs. However, there are reports about the spread of this type of cancer to other parts of the body. Although most patients are diagnosed when the tumor is localized to the prostate, in about 25% of patients, the disease is diagnosed when metastasis has occurred. Some markers can assist physicians in the diagnosis of this disease, such as the Prostate Health Index and the 4 K score. Key Clinical Message The diagnosis of prostate cancer should be considered in all age ranges of adult men. The long‐distance metastasis might cause unusual presentations of the disease, such as neurologic, musculoskeletal, and dermatologic symptoms and signs far from the origin of the cancer, before genitourinary manifestations. It is crucial to keep the diagnosis of prostate cancer in mind for men with suggestive signs and symptoms that are not usually detected in this disease.


| INTRODUCTION
Prostate cancer is one of the two most common noncutaneous cancers in men and the fifth main cause of death among both genders in the world. 1 Although the risk of occurrence of this cancer is correlated with aging, the diagnosis of early prostate cancer has had an increasing trend during the past decade, which can be attributed to the emergence of screening methods. 2 Screening tests such as Prostate Specific Antigen (PSA), have decreased the percentage of metastatic cancer and this cancer's mortality rate. 3On the contrary, the low specificity of this test has caused a large number of unnecessary biopsies.That's the reason new models of screening have been evaluated and considered recently. 4These efforts have resulted in the introduction of new markers such as the Prostate Health Index (PHI) and the 4K Score.These markers have revealed promising performance and accuracy in recent studies. 4,5one is a preferential site of metastasis in prostate cancer metastasis, with synchronous involvement most commonly in the lungs and liver. 6][9][10][11] However, this case seems to be unique due to the neurologic and musculoskeletal presentation of the disease far from the pelvis in a relatively young patient, which resulted in the misdiagnosis of multiple sclerosis and the wrong treatment for more than 5 years.

| CASE PRESENTATION
A 44-year-old male came to our tertiary outpatient urology clinic with complaints of hip pain and the inability to bear weight on the lower limbs for several months, in addition to right shoulder pain.There was no history of trauma or other systemic symptoms.He had been treated for the diagnosis of Multiple Sclerosis for more than 5 years.The pain was not responsive to non-steroidal anti-inflammatory drugs (NSAIDs) and other painkillers.The physical examination was abnormal and revealed muscle weakness and lower limb claudication.A transrectal prostate examination revealed an asymmetrically enlarged prostate.The PSA level was 258.3 ng/mL (normal range:0-4 ng/mL).Due to a rare manifestation of prostate cancer at this age, the patient was diagnosed with acute prostatitis and recommended to take prescribed antibiotics for 2 weeks.Three weeks later, the patient came back without any improvement in his symptoms.Rechecking the PSA level, the result showed 435.1 ng/mL.With the initiative diagnosis of prostate cancer, a bone scan and prostate biopsy (under the guidance of transurethral ultrasonography) were requested.The whole-body bone scan showed multiple focal areas of abnormally increased radiotracer uptake in the right clavicle and shoulder, right scapula, sternum, several ribs, pelvic bones, femur, many vertebral bodies, and skull.
The differential diagnoses considered were metastatic cancer and multiple myeloma.Ultrasonography of the prostate showed an enlargement measuring 45 mL in volume.Further laboratory investigations were suggestive of high alkaline phosphatase levels (146 U/L, normal range: 30-120) and normal calcium, phosphorus, 25(OH)vitamin D3, and parathyroid hormone levels, excluding bone diseases.The prostate biopsy results confirmed prostate adenocarcinoma in all 12 samples taken from the prostate.Gleason Scores: a range between 4/5 + 3/5 = 7/10 and 5/5 + 5/5 = 10/10 was reported (Figures 1 and 2).The percentage of involvement with tumors in samples varied from 10% up to 90%.Considering the pathology results, a pelvic CT scan and a positron emission tomography (PET) (Figure 3) scan were ordered, which showed several prostate-specific membrane antigens (PSMA)-positive pelvic lymph nodes (green arrow) along with numerous skeletal lesions in the vertebrae (red arrow), ribs, and scapula (blue arrow).The final diagnosis was advanced metastatic prostate adenocarcinoma with multiple skeletal and lymph node metastases.Because of multiple metastatic lesions, the patient's treatment started with Docetaxel and Zoladex (LHRH analogous) every 3 months and testosterone-suppressing tablets (Abiraterone) 1 gram daily.The patient's ambulation and pain have improved significantly after the initiation of the treatment.The progression and improvement of the condition have been regularly monitored clinically, along with laboratory reports F I G U R E 1 Prostate biopsy, adenocarcinoma (optical microscopy, hematoxylin, and eosin staining, 100× magnification).and imaging.The reevaluation by the neurologist was requested for the initial diagnosis of multiple sclerosis by referral of the patient.It revealed that the patient had no signs or symptoms of this disease, and there were no indications for further evaluation.

| DISCUSSION
Prostate cancer is one of the two common causes of cancer in men and the overall fifth-leading cause of death among both genders.3][14][15] Also, aging correlates directly with the incidence and mortality of prostate cancer worldwide.The average age of diagnosis is reported to be 66 years old.The joint regression analysis showed a significantly increased rate of incidence in all age groups, in contrast with declining mortality rates in these age groups over the past three decades.Prostate cancer's incidence rises significantly from 40-to 44-year-old men (less than 1 in 100,000 men) to the 45-to 49-year-old age group (more than 3 in 100,000 men).Several studies showed men in the age range of 40 and 79 years old have an increasing trend in both incidence and mortality with advancing age. 16here are several steps in the process of malignant transformation from a normal prostate to metastatic cancer, initiated as prostatic intraepithelial neoplasia (PIN), followed by localized prostate cancer, and then advanced prostate adenocarcinoma with local invasion, resulting in metastatic prostate cancer. 17In contrast with the good prognosis and high long-term survival of prostate cancer localized to the gland, metastatic prostate cancer is mostly incurable despite treatments that approach several different targets. 18The main cause of death due to prostate cancer is metastasis and involvement of other organs.The first and most common metastasis site is regional lymph nodes. 19Other common sites of metastasis include the liver, lungs, and bones, which cause osteoblastic mixed with osteolytic lesions.Bone metastasis can cause hypercalcemia, frequent fractures of the bones, and severe pain. 18arly-onset prostate cancer seems to be underestimated.However, recently, due to more common screening and increasing prevalence, about 10 percent of diagnosed prostate cancer is in men ≤55 years old.The main reason for changing the epidemiology of prostate cancer toward incidence in younger age groups can be attributed to PSA-based screening. 2Evidence of this trend is rare reports of metastatic prostate cancer in younger men, such as the 40-year-old man with testicular metastasis of prostate cancer 20 and also a 28-year-old man with metastatic prostate cancer with involvement of pelvic lymph nodes. 2 However, the case presented in this report demonstrated unprecedented, vastly metastasized prostate cancer to vertebral and shoulder bones with a significantly high level of PSA.The important point in this case is the manifestation of the disease, which was mainly upper and lower limb bone pain and walking difficulty without significant genitourinary symptoms.Although Sahil Gupta et al. believe PSA levels cannot be a good sign of prostate cancer in men younger than 50 years old due to poorly differentiated   20,21 The management of patients with prostate cancer differs based on the extent of the disease, the patient's condition, and their age.For older patients with a lower life expectancy, the wait-and-watch method seems appropriate.However, younger patients without involvement of other parts of the body are mainly treated with radical prostatectomy if they wish and have the conditions appropriate for surgery.In contrast, those with involvement in lymph nodes that are detected on imaging should be treated with androgen deprivation therapy (ADT).This can be done either with bilateral orchiectomy or medication (such as Zoladex in this patient).New drugs, many of which are informed by different genomic pathways, are under development.Parallel to the recent development of locoregional therapies for metastatic cancers, patients' conditions are managed more effectively by applying existing therapeutic options. 22Two-year follow-up imaging and laboratory data showed our patient was appropriately managed with ADT and the disease was controlled despite advanced metastasis.

| CONCLUSION
Prostate cancer's initial manifestation might be completely distinct from genitourinary system symptoms or with unusual presentations in this system as reported in previous literature (Table 1).These patients might be wrongly referred to neurologists and orthopedic surgeons.Moreover, prostate cancer should not be excluded in younger patients with symptoms alarming this disease.Although PSA might not be an excellent indicator and screening test for highly probable prostate cancers due to lower levels of this marker secreted by poorly differentiated prostate cells, considering available screening options, this specific antigen seems to be the best screening tool for prostate cancer, even in younger patients.

F I G U R E 2
Prostate biopsy, adenocarcinoma (optical microscopy, hematoxylin and eosin staining, 200× magnification).F I G U R E 3 Positron emission tomography (PET) scan, several (PSMA)-positive pelvic lymph nodes (green arrow) along with numerous skeletal lesions in the vertebrae (red arrow), ribs, and scapula (blue arrow).T A B L E 1 Uncommon presentations of prostate cancer in other literature.

Article and authors Age Presentation Treatment/Progression or remission of the disease
2f the prostate,2this case showed that even in patients younger than 50 years old, PSA can be one of the means of diagnosis, determining the progression and prognosis of prostate cancer.Ethan M. Lange et al.'s findings demonstrated the more important role of genetic factors in the occurrence of early-onset prostate cancer in comparison with later-onset cases. adenocarcinoma